Graham C.R. Ellis-Davies, Ph.D.
Associate Professor

Ph.D. (1982) Reading University
Phone: 215-762-8794
Email: medcolpa@yahoo.com

Light as sensor and actuator

Light has been used to study cells since their discovery at the end of the 17th century. The development of modern ultrafast lasers and transgenic fluorescent proteins provides the means to monitor (sub)cellular events in vivo. Such microscopy allows us to see into the brain at chosen intervals without disturbing it. Detection is so sensitive we can repeatedly pick out single synapses. Our approach is just like like taking daily (or weekly) photographs of a plant coming into bloom: time-lapse snap-shots enable you to construct a picture of the build up of a complex system step by step, in real time. We are currently applying this method to murine models of Alzheimer's disease, in order to study the causes and consequences of neurodegeneration during disease progression.

A second line of research is the use of light to control cell function. We use organic chemistry to construct photochemically labile molecules (caged compounds) that disgorge their contents upon illumination, so activating a selected biological target. We are privileged to collaborate with several labs around the world that use caged compounds to study cellular function. By far the most significant of these collaborations is with Haruo Kasai (University of Tokyo), with whom we have been interacting since 1997. In 2004 I became a member of the Institute of Neurological Sciences at the University of Pennsylvania.

Recent publications:

Tanaka, J., Horiike, Y., Matsuzaki, M., Miyazaki, T., Miyazaki, T., Ellis-Davies G.C.R. and Kasai, H. Protein synthesis and neurotrophin dependent structural plasticity of single dendritic spines” Science 319, 1683-1687 (2008). [Selected for Science Express (28 February) and a Perspective (21 March)]

Honkura, N., Matsuzaki, M., Noguchi, J., Ellis-Davies, G.C.R. and Kasai, H. The subspine organization of actin fibers regulates the structure and plasticity of dendritic spines. Neuron 57, 719-729 (2008).

Tanaka, K., Khiroug, L., Santamaria, F., Doi, T., Ogasawara, H., Ellis-Davies, G.C.R., Kawato, M. and Augustine, G.J. Calcium requirements cerebellar long-term synaptic depression: a role for a postsynaptic leaky integrator. Neuron 54, 787-800 (2007).

Ellis-Davies G.C.R., Matsuzaki, M., Paukert, M., Kasai, H. and Bergles, D.E. 4-Carboxymethoxy-5,7-dinitroindolinyl-Glu: an improved caged glutamate for expeditious ultraviolet and 2-photon photolysis in brain slices. J. Neurosci. 27, 6601-6604 (2007).

Ellis-Davies, G.C.R. "Caged compounds: photorelease technology for control of cellular chemistry and physiology." Nature Methods 4, 619-628 (2007).

Momotake, A., Lindegger, N., Niggli, E., Barsotti, R.J. and Ellis-Davies, G.C.R. "The nitrodibenzofuran chromophore-a new caging group for ultra efficient photolysis in living cells." Nature Methods 3, 35-41 (2006). [Rated "must read" in Faculty of 1000, and highlighted in both Nature and Science]

Matsuzaki, M., Honkura, N., Ellis-Davies, G.C.R. and Kasai, H. "Structural basis of functional synaptic plasticity in single dendritic spines." Nature 429, 761-766 (2004). [Rated "exceptional" in Faculty of 1000 by both Tim Bliss and Jon Lisman]

Vist the Ellis-Davies lab web site for more details.